Delivering the Right Amount of Care – Sometimes Less Is More
AbstractNew technologies utilized in clinical practice offer improved tools for diagnosing and treating patients. In some cases, these improvements cause unintended consequences by leading to the diagnosis of indolent or otherwise clinically-irrelevant disease. In my first two chapters, I examine technological advances in screening and diagnosis that have led to questions regarding whether it is necessary to treat disease at as early a stage as it is possible to diagnose it. I conduct cost-effectiveness analyses to determine whether application of less-intensive clinical regimens leads to better and more cost-effective outcomes for patients with thyroid and prostate cancer. In these two cases I find that less intensive therapeutic options provide better results. In my third chapter, I use electronic medical records data to examine a case where old technology is sufficient to identify disease at a stage suitable for the application of well-established and highly efficacious treatments. In contrast with thyroid and prostate cancer, I find that a significant proportion of patients eligible for hypertension treatment are not treated, despite simple criteria for diagnosis, low-cost therapies and clear recommendations for their use within well-established and accepted guidelines.
In Chapter One, I evaluate prostate cancer, a disease which is expected to be diagnosed in approximately 161,000 men in the United States in 2017, making it the third most frequently diagnosed cancer. In the early 1990s, rates of prostate cancer diagnoses in the United States increased dramatically due to broader use and widespread adoption of the prostate-specific antigen (PSA) test. Although these diagnosis rates peaked in the mid-1990s, today, rates remain elevated by about 50% compared to pre-PSA-testing levels. Despite this, mortality rates have remained nearly constant, suggesting that many patients identified through PSA screening may represent "over-diagnosed" or “over-treated” patients. Over the past 15 - 20 years clinicians have developed and tested less intensive, yet highly effective Active Surveillance treatment regimens. These regimens offer patients who satisfy a very specific set of criteria an option to delay immediate radical treatment, thereby avoiding the morbidities that are associated with surgery, chemotherapy or radiation therapy. Several variations of Active Surveillance have been practiced in different centers around the world, but there is no clear consensus regarding which is best, and for which patients. In my first chapter I undertake a systematic literature review to identify variants of Active Surveillance, identifying three frequently reported variations representing a high, medium and low-intensity protocol. I then undertake a decision analysis to compare these to the existing radical treatment mix that is practiced in the US. I find that Active Surveillance of medium intensity utilizing biopsy intervals of between 18 – 24 months is the most efficient option. It allows men with low-risk prostate cancer to achieve an additional 217 quality-adjusted life days at an incremental cost of just over $2,000, making it a highly cost-effective strategy. I also find that a modified version of this protocol using biopsies at ≥ 3 year intervals is more efficient, but may be less desirable to clinicians due to its longer period between surveillance biopsies and its lack of widespread clinical use.
In Chapter Two, I examine thyroid cancer. Similarly to prostate cancer, diagnoses of thyroid cancer have increased dramatically in the past 15 years, yet mortality has remained low and nearly constant. In this chapter I conduct a cost-effectiveness analysis focusing on treatment for patients with papillary thyroid carcinoma, a subtype of thyroid cancer that accounts for approximately 85% of the nearly 56,000 incident cases expected in 2017 in the United States. In the most recent (2015) update to the American Thyroid Association (ATA) "Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer", the ATA recommended two major changes to their 2009 guidelines. First, that patients with specific tumor characteristics could be treated with lobectomy, a less intensive surgery than the prevailing surgery, total thyroidectomy. Second, for patients with specific nodule/tumor characteristics, Active Surveillance of their cancer via annual ultrasound imaging was a viable option. For my second chapter, I created a Markov microsimulation model to determine whether these major changes to the guidelines improved outcomes, decreased costs, or both, for patients with papillary thyroid carcinoma. I find that the 2015 guidelines represent a dominant treatment strategy compared to the strategy recommended in the 2009 guidelines. Even after allowing for uncertainty via deterministic and probabilistic sensitivity analysis the 2015 strategy remains dominant, or at worst, highly cost-effective in expectation.
In my third chapter, I utilize a national electronic medical records database to evaluate physicians' behavior regarding rates of prescription for pharmacologic therapies to treat hypertension. Unlike prostate cancer and thyroid cancer where chapters 1 and 2 indicate that there is overtreatment, hypertension presents a contradictory case where there appears to be significant undertreatment. In 2003, the "Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" issued its 7th revision of the guidelines for the diagnosis and treatment of hypertension (JNC7). Within these guidelines, the JNC provided clear blood pressure thresholds of 140mmHg systolic and 90mmHg diastolic for the initiation of hypertension treatment and specified appropriate pharmacologic therapies. I utilized electronic medical records data from approximately 50 million patients during 2010 - 2013 from across the United States. Using these data, I determine how often pharmacologic treatment was consistent with that which would be expected if the recommendations of the JNC7 guidelines were followed for those patients. I find that the majority of patients meeting the JNC7 systolic and diastolic blood pressure criteria for treatment do not receive a prescription as recommended by the JNC7 guidelines. Secondarily, the rates of treatment and guideline concordance vary by age, race, and sex. Through the use of logistic regression analysis I determine that patients satisfying the JNC7 criteria for systolic blood pressure have odds of treatment of 2.98 compared to those who do not, but that for patients with systolic blood pressure readings near the threshold of 140mmHg the odds of treatment for those who satisfy the JNC7 criteria increase to 7.75. From these results, I infer that the JNC7 guidelines successfully stimulate treatment of patients who satisfy the criteria defined in the JNC7, but that there is still significant undertreatment of eligible patients.
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